A series of polysubstituted and fused heterocycle derivatives of acylthiourea was prepared and the biological activity against influenza virus was evaluated. Of the analogues that demonstrated IC(50)s<0.1 microM, acylthiourea derivatives 16 and 50 were further investigated as candidates with the most potential for future development. The SAR of these compounds are discussed and they represent a novel class of highly potent and selective inhibitors of influenza virus.